A Study to Evaluate Safety and Exploratory Efficacy of KTP-001 in Subjects With Lumbar Disc Herniation

A Study to Evaluate Safety and Exploratory Efficacy of KTP-001 in Subjects With Lumbar Disc Herniation

Open-Label, Non-controlled, Single Ascending Dose Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Exploratory Efficacy of KTP-001 in Subjects With Lumbar Disc Herniation

The purpose of this study is to evaluate the safety and exploratory efficacy of KTP-001 in subjects with lumbar disc herniation.

This study was a first-in-human, open-label, non-controlled single ascending dose study of KTP-001 in male and female subjects between the ages of 30 and 70 years with a single herniated lumbar disc. After obtaining informed consent, subjects were evaluated during a screening period of no more than 3 weeks (21 days). This study was conducted in 10 centers in the US. Subjects that met all screening requirements and inclusion criteria and none of the exclusion criteria were enrolled into the study. Overall, 24 subjects were enrolled and treated: 6 subjects in each cohort. Cohort 1 received a 5 μg/disc dose of KTP-001 by intradiscal injection. Following administration of study drug, subjects were confined to the study center for 24 hours to collect data for safety and efficacy measures and collect blood samples for safety, PK evaluation, exploratory PD and anti-KTP-001 antibody and then returned for further assessments at various intervals from weeks 1 through to month 24. After all subjects in Cohort 1 had received study drug, safety measures were evaluated by a Data and Safety Monitoring Board (DSMB) to determine whether to escalate KTP-001 administration to the next dose level. If appropriate, Cohort 2 subjects received 15 μg/disc of KTP-001, Cohort 3 subjects received 50 μg/disc of KTP-001, and Cohort 4 subjects received 150 μg/disc of KTP-001 by intradiscal injection. All safety, PK, and exploratory efficacy assessments were performed for the subjects in the subsequent cohorts as were performed for Cohort 1.

Safety Assessed by Adverse Events, Magnetic Resonance Imaging (MRI), X-ray Imaging, Physical Examination, Neurologic Examination and Vital Signs

Any clinically significant changes were recorded as adverse events. They are described in the adverse events section of the results. AEs related to MRI, X-ray Imaging, Physical examination, and Neurologic examination are considered as adverse events of special interest (AESI). A treatment-emergent AE (TEAE) was defined as an AE that was not present prior to treatment with study drug, but appeared following treatment or was present at treatment initiation but worsened in severity during treatment.

Number of Participants With Change in 12-lead Electrocardiogram (ECG) and Clinical Laboratory Tests (CLT)

Assessment of the number of participants with change in 12-lead ECG and CLT were assessed from baseline, 24 hours and 13 weeks.

The serum concentrations of KTP-001 were below the limit of quantification (BLQ) (<100 ng/mL) at all time points in all participants

Lower back and leg pain were assessed using an 11-point numerical rating scale (0 = "no pain" and 10 = "worst possible pain"). The endpoint was mean change from baseline at 6 and 13 weeks post-dose; with a negative number suggesting an improvement in pain while a positive number suggests a worsening in pain.

Number of Participants With Changes to Spinal Flexion and Tension Using the Straight-Leg Rising and/or Femoral Stretch Test

The changes to spinal flexion and tension were assessed using Straight-Leg Rising (SLR) and Femoral Stretch (FS) tests which are on a scale of no change, positive to negative or negative to positive and where a positive result for SLR may indicate between 30 and 70 degrees, where a positive result for FS may indicate pain in the anterior thigh of the test leg and the elicited pain.

The Oswestry Disability Index (ODI) score is calculated as participant score divided by possible score multiplied by 100, where the following scores can be interpreted to indicate: 0-20% = Minimal disability; 20-40% = Moderate disability; 40-60% = Severe disability; 60-80% = Crippled; 80-100% = Bed bound;

The endpoint was change from baseline at Week 6 and 13 hours post-dose. The Short Form-12 (SF-12) is a Quality of Life questionnaire which measures functional health and well-being from a participant's perspective across eight health domains. Each participant answers questions on a 5-point Likert scale, which rates responses according to how much the participant agrees or disagrees with a particular statement on their health and wellbeing, including vitality/physical functioning/bodily pain/general health perceptions/physical role functioning/emotional role functioning/social role functioning and mental health. Each scale is transformed into a 0-100 scale, assuming each question carries equal weight. Lower scores mean greater disability and higher scores mean less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.

The Patient Global Impression Change PGI-C scale was used where the scale ranges are from 1 (no change or condition has got worse) to 7 (a great deal better, and a considerable improvement). The endpoint was the value at 6 and 13 weeks post-dose.

The endpoint was change from baseline at 6 and 24 hours post-dose, and at the 1-, 2-, 4-, 6-, and 13-week follow-up visits or early termination visit.

Inclusion Criteria: Subject has had a single contained or noncontained (extruded) lumbar disc herniation (L3-L4, L4-L5 or L5-S1) diagnosed by clinical symptoms and/or physical findings and confirmed by MRI. Subject has leg pain with a documented positive straight leg raise (SLR) test or femoral stretch test (FST). Subject has experiences herniated disc symptoms for at least 6 weeks prior to the study without relief with pain medications and other therapies. Subject has a BMI of 18 to 35 kg/m2 Exclusion Criteria: Subject has a sequestered lumbar disc herniation or intrathecal herniation confirmed by MRI Subject has two or more symptomatic lumbar disc herniations Previous intradiscal therapeutic intervention or has had any lumbar surgery Presence of lumbar spine disease and/or deformity other than a lumbar disc herniation Active smoker or is unable to abstain from tobacco use for 2 weeks prior to study injection Subject has a history or presence of significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, or psychiatric disease